The OBR Blog

San Diego, CA—Data presented at the American Society of Hematology
suggest that the antibody conjugate drug, gemtuzumab ozogamicin (Mylotarg; Pfizer)—once approved for use in acute myeloid leukemia (AML) in 2000, and then voluntarily pulled from the market in 2010 due to post-marketing evidence of lack of efficacy, as well as unacceptable toxicity—may have a shot at a second coming.

Sylvie Castaigne, MD, of the Hôpital de Versailles in France, and lead investigator from the Acute Leukemia French Association (ALFA) study, detailed how she and her colleagues use a fractionated dosing regimen for Mylotarg—one that would limit toxicity, thereby allowing for its use in combination with standard chemotherapy which would boost overall efficacy.

Dr. Castaigne was able to perform the study because Mylotarg is still available in France under the limitations of compassionate use. “But using the standard dose of 9mg/m2, the drug could not be combined with chemo,” she said. By dosing the drug in three increments of 3mg/m2 over a week’s time, a combination with chemotherapy was enabled.

The trial included 278 AML patients, ages 50-70 years, who were randomized to one of two treatment arms of standard chemotherapy (60 mg/m2 of daunorubicin for three days and 200 mg/m2 of cytarabine for seven days) with or without fractionated Mylotarg. Patients were followed for three years.

Results showed that the median event-free survival time was 19.6 months in the Mylotarg arm vs 11.9 months in the chemotherapy alone arm. Overall survival was also improved significantly in the Mylotarg arm, with a median overall survival of 34 months vs 19.2 months in the chemotherapy alone arm. Adverse events were substantially lower than those historically observed with the 9mg/m2, single dose infusion of Mylotarg.

All this puts Pfizer in an awkward position. “I’ve been aware of Dr. Castaigne’s work for quite some time,” said Mark Shapiro, MD, head of Global Medical Affairs for hematology programs at Pfizer Oncology. “It’s extremely exciting. I’ve been working on this compound for several years and not just these, but other data presented at the conference are quite impressive.”

Two other unrelated studies using the fractionated dosing regimen in AML were presented with both reporting data in support of this new approach.

Where do we go from here?

The way forward, however, is not so clear. Only one other drug has plied these regulatory waters. Many healthcare stakeholders had clamored for Iressa to be pulled from the market for poor efficacy, and side effects, but in the end the FDA chose to make it available on a highly restricted basis. Like Mylotarg, Iressa had been the beneficiary of an accelerated approval.

Is there any other precedent for bringing a dead drug back to life? “I don’t know,” said Dr. Shapiro. “First we need to assess the quality of the data and determine if the results are truly robust; then we’ll sit down and have a conversation with the regulatory authorities to see if there is a path forward. “

Suffice it to say that for now, there’s an elephant in the room, as noted by, Susan O’Brien, MD, Professor, Department of Leukemia, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX. “There are actually three presentations with Mylotarg here – the (ALPHA study) was in the plenary session because the data was the most impressive. It clearly showed a dramatic improvement – not in CR rate, which is consistent across all the trials – but for event-free survival (EFS). The arm with Mylotag had a 2 year EFS of 45% vs. 15% without it.”

Assuming this clinical success can be validated, Dr. O’Brien wonders about the business angle. “It’s a rather small market for Pfizer (perhaps $100 million or so). Would they sell it? Or would someone else come in that might be interested?”

And as far as a regulatory precedent… “There are drugs that have been approved and then pulled, Avastin of course, but I’m unaware of any drug that was pulled and then later re-introduced. I have no idea what the mechanism of going about that would be,“ said Dr. O’Brien, “But it’s very hard to ignore these data.”

The Cancer Center Business Summit (http://www.CancerBusinessSummit.com) is a nationally recognized educational resource which deals with oncology/cancer care delivery, oncologist-hospital alignment and integration, and the business, legal, and financial models associated with such initiatives.

Each year, in conjunction with its annual conference, the Summit conducts a research survey of current trends affecting the oncology/cancer care sector. In keeping with this year’s theme, Achieving Accountable Cancer Care, the 2011 survey explored the positioning and payment re-design for oncology services within accountable care initiatives, whether such initiatives are in direct response to federal health reform (accountable care organizations – ACOs) or otherwise.

Phone interviews were conducted with 36 pre-qualified healthcare organizations to identify:
• The structuring/positioning of oncology services within integrated and ACO-like organizations and
• Payment/reimbursement re-design methodologies being undertaken in oncology

Key Findings from the Survey

1. In the context of ACO planning, oncology/cancer services are not considered an organizational priority for achieving cost savings compared to other chronic health conditions, for example, diabetes, chronic obstructive pulmonary disease (COPD) or heart disease.

Reasons cited were:
• Oncology too complex with a wide range of cost variability and unpredictability
• No clear definition of what constitutes cancer care
• Difficulty in segregating cancer-related costs from other costs for cancer patients with co-morbidities
• ACO principles are derived from primary care experience resulting in familiarity and predictability in non-cancer diseases

2. Despite low priority attention in the context of ACO planning, commercial payers are actively pursuing non-traditional and innovative methodologies for payment re-design for oncology services, typically at the community oncology level.

Much of this interest in bending the cost curve has surfaced within the last 6 months. Local and regional initiatives in oncology payment re-design are underway with United Healthcare (5 demonstration sites nationally), Aetna and a variety of Blue Cross plans, including oncology-specific payment re-design projects identified in Maryland, New Jersey, Tennessee, Michigan, Indiana, South Carolina and Southern California.

3. Re-design methodologies are focusing on drug cost reduction achieved through clinical pathways compliance. The predominant model has been to compensate oncologists at a premium for compliance with agreed upon clinical pathways. Typically, 80% compliance results in enhanced reimbursement and non-compliance results in penalties.

4. Trends are emerging to incorporate programs that result in reduced treatment-related emergency room visits and hospitalizations, and in rationalized end-of-life planning—all features of the so-called “oncology medical home” model.

A new sub-industry has surfaced to serve as middlemen in matching health plans with oncologists in transforming to the new oncology accountable care processes. Current front runners in this “match making” business include Aetna (through its acquisition of Medicity), Cardinal P4 and Proventys (through its affiliation with NCCN).

5. Despite the initial lack of interest in oncology as foundational to an ACO, community oncologists should not be discouraged. A viable strategy is “watchful waiting,” that is remain attuned but uncommitted to any ACO dynamics taking place in the local market.

In the interim, take the initiative with other like-minded oncologists to organize to scale as a specialist “neighbor” to someone else’s ACO. One example of organizing to scale is for oncology practices to develop regional, clinically-integrated oncology networks based on the care process transformation and payment re-design principles of the oncology medical home model.

Trends to Watch for Moving Forward into 2012

1. Expect to see an acceleration in health plan experimentation beyond pathways with programs that incorporate care processes to manage ER utilization, hospitalization and advance care planning—the features of the oncology medical home model.

2. Expect to see increased interest in oncology practices organizing to serve as specialist “neighbors” of primary care medical homes—the building block of ACOs.

3. Expect to see renewed interest in compatible oncology practices organizing to scale as clinically integrated oncology networks with common treatment pathways and third party health information exchanges (HIE) bringing data connectivity and advanced informatics and reporting capabilities to such networks.

4. Watch for oncology “bundled pricing” as the next oncologist-hospital alignment frontier. The recently announced CMI “Healthcare Innovation Challenge” may be a potential foot-in-the-door with Medicare in this regard.

By:
Ronald Barkley, MS, JD is President of Cancer Center Business Development Group and Co-Founder and Co-Chair of the Cancer Center Business Summit. Mr. Barkley can be reached at 603.472.2285 or rbarkley@ccbdgroup.com.